Cells of the Nervous System Flashcards
Role of neurons
Receive, integrate and transmit information in the nervous system.
Neuroglia (glia)
Supporting cells for neurons (“glue”)
What are the historical approaches of studying the brain cells? Were these approaches effective?
- Use different stains to reveal histology of different cells. In particular, stains that label nuclei - Hematoxylin and eosin stains.
- These stains reveal cell bodies and diffuse neurophil (layout of cell bodies).
These stain do not give you much information about complex morphology, fine processes of neurons.
Stains were poor at revealing the complex wiring and connectivity of the brain which is its most important feature.
Golgi Vs Cajal: what stain did they look at?
Golgi and Cajal looked at the exact same thing: the silver impregnation stain and concluded/ saw two different things.
What was Golgi’s conclusion? What was the name of his theory?
Golgi’s “black reaction” - attempted to stain the dura (surface of the brain), did not work and instead gave the silver impregnation stain which had an amazing labelling of individual cells (see cells in entirety, all the fine processes of the dendrite). Only 1 in 100 cells of the tissue ended up getting labelled.
Golgi looked at the picture of the silver impregnation stain and saw this network of fibres, all interconnected. From this he decided that it was evidence that the entire nervous system functions as a unit.
i.e the nervous system was a network of fibres that was not made up of individual neurons.
He came up with the Reticular Theory.
What was Cajal’s conclusion? What was the name of his theory?
Cajal saw the exact same picture and concluded the nervous system is actually made up of individual units. The individual unit of the nervous system is the single neuron (neuron doctrine).
- Responsible for neuron theory of the brain: the idea that the brain is made-up of lots of individual cells rather than just wires.
- Did anatomically precise drawings.
- Looked at tissue and inferred function from the structure. Inferred structure-function relationship.
Dendrites = web reaching out to take in information. Axons = Processes extending out from the cell.
What are the Four principles of the neuron doctrine?
- The brain cell (neuron) is the unit of the nervous system (neuron = elementary signalling unit of nervous system).
- Neurons are separated by “gaps” (small point of contact = synapse) through which they communicate.
- Connection Specificity - each neuron contacts only specific target cells (each neuron has a set of preferred connections).
- Dynamic Polarization - Impulses travel in one direction in a neuron.
Why is it named the synapse and who named it?
Syn (together) and haptein (clasp) - the thing that holds cells or neurons together.
Charles Sherrington named it.
What is the evidence argued for chemical transmission at the synapse rather than electrical?
- Information flows in one direction from axon of one cell to dendrite of another cell.
- Evidence that some interactions can be inhibitory rather than excitatory.
- A delay of several milliseconds are present, even in very simple reflex arcs made up of just a few synaptic links.
How do synapses work?
Synapses are chemical reactions.
- Presynaptic terminal releases a chemical, a neurotransmitter, upon the arrival of an electrical signal.
- The neurotransmitter is detected by the post-synaptic cell, which respond by reproducing a chemical reaction causing the electrical signal to be generated.
Electrical signal converted to chemical signal, which is then converted back to an electrical signal.
What is a “true” electrical synapse?
Axon contacts the dendrite of a cell and instead of having a release site for neurotransmitter they actually form little channels that connect the two cells together. So, ions can flow through the little channels into the postsynaptic cell.
These are more common in invertebrate nervous system.
What is the difference between chemical and electrical synapse?
Chemical synapse: can have inhibitory signal
Electrical synapses: Cannot have inhibitory signal, much faster, high fidelity transmission
General anatomy of a synapse
Pre synaptic side: can figure out which one it is based on all the docked vesicles floating around.
Post synaptic side: can be visualized in an electron microscopy image because of the post synaptic density (PSD) - extremely dark region.
They are important for neurotransmission.
Name excitatory neurotransmitters
- Acetylcholine
- Glutamate (majority of excitatory neurons in CNS mammals depend on glutamate)
Name inhibitory neurotransmitters
- GABA (main inhibitory neurotransmitter): capable of converting a positive signal into an inhibitory postsynaptic potential (more negative membrane potential) and inhibits activity in the postsynaptic cell.
- Glycine: less prevalent found in older brain structures.
What are neuromodulatory neurotransmitters? Give some examples.
- May release and change the excitation of the post synaptic cell.
- May work by bulk transmission: neurotransmitter just gets dumped into the extracellular space and binds receptors on a number of postsynaptic cells to change their response.
- More modulatory
Examples:
Acetylcholine, Serotonin, Noradrenaline, ATP/Adenosine, Dopamine, Neuroactive peptides
What are the 4 compartments of a neuron?
- Input compartment: dendrites and soma (postsynaptic)
Excitatory and Inhibitory inputs onto dendrites and cell body. Spines receive mainly excitatory inputs while the soma receives mainly inhibitory inputs.
- Integrative compartment: soma and axon initial segment (axon hillock)
Passively propagated signals are integrated in the cell body. Action potentials are usually generated at the axon hillock. Summation of those inputs change the membrane potential of the cell, causing it to either become more depolarized or more hyperpolarized.
- Conductile compartment: axon
Action potential conducted in all or none fashion.
- magnitude of signal encoded by frequency
- speed of transmission dependent on axonal diameter and myelination.
- Output compartment: Axon terminal (synapses) (pre-synaptic)
Action potential in nerve terminal causes release of chemical neurotransmitter
Identify the parts of the neuron and the 4 different compartments.
What is the most popular way of characterizing cells?
Transcriptomic analysis
Unipolar cell
- There is a soma (cell body) and one extension that goes out (axon) - both receive and send information.
- Seen extensively in invertebrate nervous system
- Minimal input branching
- High fidelity information transfer (eg: sensory transmission)
“information highway” - doesn’t pass through the soma (aka the city)
Bipolar cell
- Cell body, one dendrite, one axon (two branches)
- Common in vertebrate brain (common in retina)
- Stuck in middle of a circuit as a way of transmitting a signal from one end to the other (funnelling info down a path)
- Minimal input branching
- High fidelity information transfer (eg: sensory transmission)
Pseudo-unipolar cells
- high fidelity information transfer
- Cell body with one extension BUT that extension breaks into two directions: one goes to innervate tissue and other goes into CNS (one process that functions both as dendrite and axon).
- Main morphology in peripheral nervous system (touch sensitive cell, pain)
- Information highway - info doesn’t even pass through cell body that much - straight to spinal cord.
What are the different types of multipolar cells?
- Motor neuron of spinal cord
- Pyramidal all of hippocampus
- Purkinje cell of cerebellum - purkinje cells are the biggest inputs cells (has the most synaptic inputs- massive accumulators of information).
Multipolar cells
- Integrate information (eg: learning and memory)
- Separated dendritic and axonal morphology
- 1 to 100 000 synapses/neuron
- The information very clearly passes through the soma and goes into an axon hillock where summation/ processing of information happens.
- These cells have multiple input compartments, many branches of dendrites, and a single axon. → Info passes through the soma, gets summated and then output through the axon to tell the downstream cell about it.
Pyramidal cell for excitatory neuron
- Excitatory neurons have dendrites which serve as their primary inputs.
- Dendrites are stubbed with filopodial protuberances called “spines”
Spines
- They are small, sharp processes coming off of a cell. Each spine reaches out and makes contact with an axon.
- Large spines indicate a location of strong synapses and strong signal. Small spine = more dynamic, weaker synapse (usually newer synapses).
- On a spine head, there is the postsynaptic density (region of high concentration of receptors) and opposed to it a presynaptic terminal (vesicles ready to release neurotransmitters).
- Spines are the majority of postsynaptic excitatory sites in the CNS.
- Typically on spines we find excitatory synapses (glutamate receptors).
Smooth dendrites
Receives synapses on the shaft
Spiny dendrites
Large projection neurons - receives synapses on the shaft as well as on the dendritic spine.
On average, there are how many excitatory synapses per spine?
one excitatory synapse per spine
Where on the cell do you usually find excitatory synapses vs inhibitory synapses?
- If you see a synapse forming on the shaft of the cell or the soma, there is a high probability of being an inhibitory synapse. NO PSD.
What is the importance of spines?
Spines are like electrically isolated compartments. There is a bit higher resistance (electrically) in the shaft of the spine than within the spine itself. So a signal that occurs within the spine will be generated more easily.
- Signal that occurs in spine is easier to change the voltage → more isolated than if it didn’t have a spine.
- Chemical reaction occurs in spine → each spine is a small biochemical compartment.
Overall, synapses that form on the shaft are less independent. They are more integrated.
What are the different forms of contacts where synapses can occur?
- axon/dendrite touch
- axon/spine touch
- bouton/dendrite contact
- bouton/spine contact
What are the two different block face EM techniques
here are two different methods of cutting:
- Using a diamond knife - cuts sample between images
Advantages:
- Don’t lose any sections
- easily aligned
- Using an Ion beam - etched surface between images
- High resolution
- perfectly aligned
What are the different morphological classes of dendritic spines and their defining characteristics?
- Dendritic filopodia: highly dynamic immature processes. These spines sample the environment then come into contact with an axon. Filopodial searching for synaptic partners: post synaptic cell is actually the active player in choosing partner. Then converts into a more stable mushroom or stubby spine.
- Thin spines: long neck with a small spine head.
- Mushroom spines: large spine head, stable, mature + strong synapse. These are good for local biochemical interactions, a kind of small compartmentalization signalling.
- Stubby spines: Short or no neck (thin) → spine head close to cell body. Very strong input onto cell, but less isolated from rest of cell.
- Forked spines: possibly splitting/adding a new synapse.
State the main differences between axons and dendrites.
Some key points:
- The axonal and dendritic compartments express a different complement of microtubule associated proteins. MAP Tau is found exclusively in axons and MAP2 is found only in dendrites.
- Dendrites have a higher microtubule to actin ration than axons.
- Dendrite microtubules have plus ends pointed in both directions while axons all the plus side points distally (towards the tip)/
Microtubules? What are the differences between microtubules that are found in the axons vs in the dendrites?
Microtubules consist of helices of 13 tubulin dimers (alpha and beta). The end with the beta-tubulin exposed is the end that can add more dimers and is called the +end. Microtubules are much bigger, transport things long distances and act as the railroad track for the cell. Direct material and organelles to and from distal end of process (structure along which things are transported down the cell)
- Axon microtubules are all oriented in the same direction. They have + ends towards the growth cone (away from cell soma) → +end is more prone to add new dimers (more dynamic). The -end is less dynamic.
- Dendritic microtubules are in both directions.
In what directions does dyenin and kinesin work in?
Dyenin moves in the retrograde direction (going backwards - from terminal to cell body).
Kinesins move in the anterograde direction (going forward - from cell body to terminal)
*Neuron direction is always considered forward as cell to axon. Information always goes from dendrite → soma (cell body) → axon.
Myelinating Schwann Cells
- Increase speed of conduction (saltatory conduction).
- One Schwann cell per axon, but one axon can be wrapped by multiple schwann cells.
- Disease caused by immune system attacking the myelin schwann cell: Guillain-Barré Syndrome (demyelination in the PNS = paralysis).
- Myelin wraps approx. 100 times with almost no cytoplasm (compact).
Saltatory Conduction
Myelin increases axonal conduction velocity
The myelinating schwann cells produce myelin along axons in the PNS which have gaps in them. The gaps are called node de Ranvier and these are very important sites of action potential regeneration and giving strength back to the action potential as it travels over a long distance.
The tripartite synapse
The functional synapse is not just presynaptic axon and postsynaptic dendrite. The associated glial process should be considered to participate as well.
